Intervention strategies to improve adherence to treatment for selected chronic conditions in sub‐Saharan Africa: a systematic review

Abstract Introduction Evidence‐based intervention strategies to improve adherence among individuals living with chronic conditions are critical in ensuring better outcomes. In this systematic review, we assessed the impact of interventions that aimed to promote adherence to treatment for chronic conditions. Methods We systematically searched PubMed, Web of Science, Scopus, Google Scholar and CINAHL databases to identify relevant studies published between the years 2000 and 2023 and used the QUIPS assessment tool to assess the quality and risk of bias of each study. We extracted data from eligible studies for study characteristics and description of interventions for the study populations of interest. Results Of the 32,698 total studies/records screened, 2814 were eligible for abstract screening and of those, 497 were eligible for full‐text screening. A total of 82 studies were subsequently included, describing a total of 58,043 patients. Of the total included studies, 58 (70.7%) were related to antiretroviral therapy for HIV, 6 (7.3%) were anti‐hypertensive medication‐related, 12 (14.6%) were anti‐diabetic medication‐related and 6 (7.3%) focused on medication for more than one condition. A total of 54/82 (65.9%) reported improved adherence based on the described study outcomes, 13/82 (15.9%) did not have clear results or defined outcomes, while 15/82 (18.3%) reported no significant difference between studied groups. The 82 publications described 98 unique interventions (some studies described more than one intervention). Among these intervention strategies, 13 (13.3%) were multifaceted (4/13 [30.8%] multi‐component health services‐ and community‐based programmes, 6/13 [46.2%] included individual plus group counselling and 3/13 [23.1%] included SMS or alarm reminders plus individual counselling). Discussion The interventions described in this review ranged from adherence counselling to more complex interventions such as mobile health (mhealth) interventions. Combined interventions comprised of different components may be more effective than using a single component in isolation. However, the complexity involved in designing and implementing combined interventions often complicates the practicalities of such interventions. Conclusions There is substantial evidence that community‐ and home‐based interventions, digital health interventions and adherence counselling interventions can improve adherence to medication for chronic conditions. Future research should answer if existing interventions can be used to develop less complicated multifaceted adherence intervention strategies.


I N T R O D U C T I O N
Patients on treatment for chronic conditions face multiple barriers to adherence, and no single intervention is deemed sufficient to ensure that high levels of adherence to treatment are maintained [1].There remains a need to strengthen and tailor different intervention strategies to different barriers to adherence for chronic conditions [1].
In the efforts to address adherence to treatment for chronic conditions; behavioural and psychological factors, education, integrated care and patient self-management interventions have been explored [2,3].This includes behavioural rehabilitation provided by health providers to patients, integration of psychosocial support within health programmes and patients' knowledge about the medication and their overall satisfaction with the treatment [4][5][6].Other studies have recommended telephonic counselling and text messaging or reminders (mobile health/mhealth), packaging/medication boxes, home visits, drug-level monitoring and consistent clinical monitoring of patients [4,6,7].Studies focusing on adherence to antiretroviral therapy (ART) for human immunodeficiency virus (HIV) have further emphasized the importance of compliance with standard treatment guidelines (monitoring and reporting of health information [data] to promote appropriate medicine use) [8][9][10].Interventions that use mobile technology (mhealth) have the potential to facilitate self-management, education and support, unfortunately, mhealth applications have been limited in sub-Saharan Africa (SSA), and they have had mixed effects on controlling non-communicable diseases (NCDs) [11,12].
Although numerous reviews have evaluated adherence interventions [12][13][14][15][16], few have undertaken a comparative analysis of adherence to medication for various conditions, notably HIV, hypertension (HPT) and diabetes mellitus (DM).While HIV remains the leading cause of death especially in young and middle-aged adults in SSA, the burden of NCDs, particularly HPT and DM, has increased rapidly in recent years [17][18][19].There has been a surge in the burden of NCDs in SSA over the past two decades, rising from 24% in 2000 largely due to challenges in the implementation of preventative and control measures including screening, diagnosis and care [20][21][22].Therefore, understanding adherence to related medication is a priority issue.This review assesses treatment adherence interventions for HIV, HPT and DM in SSA, which provides valuable comparisons and context to adherence intervention strategies for chronic conditions in SSA.We sought to understand evidence-based approaches to support adherence to treatment for HIV, HPT and DM.

M E T H O D S
This systematic review has been designed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) [23] (Supplementary Material 1), following the registered protocol on the International Prospective Register of Systematic Reviews (PROS-PERO) (registration number: CRD42019127564) [24].The study used Population (P), Interventions (I), Comparisons (C) and Outcomes (O) (PICO) criteria as the search strategy tool.

Eligibility criteria
All studies assessing the impact of adherence interventions for ART, anti-hypertensive medication and anti-diabetic medication in SSA that were conducted or published between 01 January 2000 and 30 November 2022 were considered for inclusion.Studies were excluded if the study setting was not SSA, if papers were written in any other language than English, if the health condition for which adherence to medication was assessed was not HIV, HPT or DM, and if the study was published before the year 2000 (Table 1).

Data collection
We conducted a systematic data search using several electronic databases, including PubMed Web of Science, CINAHL, Scopus and Google Scholar, between 01 August 2021 and 29 February 2024 (including the period when the analysis was updated: 08 February 2024−29 February 2024).These dates included repeat searches in case of article publications occurring after the initial search.We also reviewed citations and bibliographies of other related reviews to identify additional relevant material.
The search terms were adjusted to suit the database being searched.An inventory with the database searched, the corresponding search criteria used, the date when the searches were conducted and the results were all maintained (Supplementary Material 2_search term strategy).Two other reviewers (Lisa Noordman and Marit Wiltink) ran the searches separately for comparison.The comparison entailed a number of articles showing as a result of each search (search hits).Small differences were observed and attributed to different dates on which databases were accessed and/or searched by the reviewers.In this case, results from each reviewer were merged and de-duplicated.
Three reviewers (S.B.G., Lisa Noordman and Marit Wiltink) independently conducted title and abstract screening.The screening results were compared for each reviewer to identify any discrepancies.Discrepancies in the screening results were discussed between the three reviewers.In cases where an agreement on inclusion could not be reached, a fourth reviewer (S.T.L.-E.) made the final decision.
From the database search engines, data were imported into the Rayyan electronic tool, a free web-tool designed to help synthesize data for systematic reviews, scoping reviews and literature reviews [25].

Study selection
The reviewers performed title and abstract screening using a predefined list of inclusion and exclusion criteria (Table 1 and Figure 1).In case the article was not specific or clear enough, especially in terms of intervention type and outcome measures, screening was discussed by all the reviewers and S.T.L.-E.made the final decision.Multiple studies of the same cohort were included if different outcomes were studied.

Data extraction
Data were extracted using a standardized form.

Quality assessment
For all studies in the systematic review, assessments of quality and risk of bias were performed using the Quality in Prognostic Studies (QUIPS) tool (Supplementary Material 3) [26].The risk of bias was assessed as low risk, moderate risk or high risk for each of the following domains: study design, participant selection, study sample size, descriptions of outcomes and description of interventions.

Data analysis
For each study included in the review, the following characteristics were recorded: authors, year of publication, country where the study was conducted, study duration, study design, study site/setting, study population/sample, sample size, sex of participants, age of participants, health condition studied, intervention assessed, outcomes analysed and main findings.Adherence interventions were described according to the type of intervention and implementation setting.

Description of included studies
A total of 32,927 records were screened and after the removal of duplicates, a total of 30,918 records remained and their titles and abstracts were screened for inclusion.Of the 30,918 records, 2814 were further screened for inclusion by abstract.The full-text screening of potentially eligible articles was subsequently done in 497 records.The reasons for the exclusion of papers are noted in Figure 1.In total, 82 articles  were found to be eligible and data were then extracted (Supplementary Material 4).Of the 82 articles, 74/82 (90.2%) were peer-reviewed journal articles, 7/82 (8.5%) were dissertations and 1/82 (1.2%) were paper abstracts.Fifty-eight papers reported studies of interventions to promote adherence to ART, six were antihypertensive medication related, 12 were anti-diabetic medication related and six focused on more than medication for more than one condition.The studies included reported findings on a total of 58,043 participants.The mean sample size was 735 participants (range: 10-10,136).The median age of participant samples was between 30 and 40 years and about two-thirds of the study participants were women.Almost half of the included studies (39/82, 47.6%) were conducted in the southern African region, with a total of 35,849/58,043 participants (61.8%), and East Africa (

D I S C U S S I O N
There has been a significant increase in the number of studies implementing and evaluating interventions aimed at

Health literacy
The achievement of a level of knowledge, personal skills and confidence to take action to improve personal and community health by changing personal lifestyles and living conditions.Note: The categorization of interventions was adapted from a study by Ridgeway et al. [13].
promoting adherence to chronic conditions.This systematic review combines the available evidence from a large number of studies to identify a range of adherence interventions aimed at promoting adherence to ART among people living with HIV, anti-hypertensive medication and anti-diabetic medication.The majority of adherence interventions described in this review were ART-related.This is consistent with health programmes in most sub-Saharan African countries that have placed more focus on HIV programmes as compared to HPT and DM-related programmes, but different to most high-income countries whose focus has been balanced across the three chronic conditions [8,[109][110][111].Individual-related characteristics described in the reviewed studies demonstrated that almost two-thirds were females and of middle age (30−40 years).The individual-specific characteristics identified may represent the demographic profile of patients in chronic treatment programmes, particularly those receiving HIV care in the SSA [112,113].
The community-based adherence interventions highlighted an important link between primary healthcare facilities or services and the communities, demonstrated integration of treatment and patient care, and decentralization of chronic care to the communities [114,115].Community-and home-based adherence interventions such as peer treatment support meet the rising need associated with overall chronic care, where due to the real shortage of healthcare workers and the growing caseload of people needing care, professional workers' roles are increasingly limited to medical and nursing tasks in health facilities [116].This review provides evidence of the efficacy of community-and home-based adherence support strategies, but more focus should be on their acceptability and cost-effectiveness.
Mobile health is increasingly being explored for health promotion [117] and was also used in adherence-promoting interventions identified in this review, to deliver educational and behavioural components, either singly or in combination.The majority of mhealth-related medication adherence interventions described in this review reported improved adherence using specified outcome measurements.Most mobile health interventions were used to educate, remind or provide advice to patients.These technologies enabled the collection and transfer of patient-specific data/information across to different professionals, who could then deliver tailored feedback and reminders to the patients.The increasing advancement in technology and related benefits received by patients from healthcare providers without presenting at a health facility is an appealing prospect.Furthermore, mhealth interventions could have a greater reach, and better adoption and implementation; thus having a greater positive heath impact [117,118].However, more research is needed to establish the sustainability of such interventions and to evaluate how mhealth interventions can be useful in the short and long term in promoting adherence to medications.
The interventions described in this review were primarily directed at patients and ranged from adherence counselling including both individual and group counselling to more complex interventions such as mhealth interventions which took into consideration patients' abilities to use digital technology and preferences in addition to educating and aiding them to adhere to medication.Some of the interventions employed a combination of interventions, for example adherence intervention consisting of a combination of educational, behavioural or affective strategies.Behavioural and effective strategies, which are increasingly being used in adherence support interventions, range from adherence aids (such as medication administration aids), to motivational interviewing [119,120].
Individual and group counselling adherence interventions could be regarded as being more patient-centred; however, their impact depends on the extent to which patients' or individuals' psychosocial needs are taken into consideration.This includes attitudes towards the health condition, cultural barriers, social concerns (such as perceived stigma) and cognitive abilities.These needs have been recognized in recent years as important predictors of optimal adherence to treatment and should be considered in any development of adherence interventions for chronic conditions [121].
The role of healthcare service-related interventions on medication adherence has been emphasized, particularly in cases of chronic diseases [122], though their impact is difficult to measure and has often been found to lack consistency [122,123].More adherence interventions have also addressed healthcare services-related factors impacting adherence, as was seen in this review.These include patientrelated, condition-related and medication-related factors.For example, this review reported that adopting and using better ART drug treatment improved adherence to medication.In addition, greater emphasis on task-shifting and decentralization of services improved medication adherence and is, therefore, worthy of further investigation.This review also reported improved medication adherence and retention in care for participants who received cash vouchers during the study period.The early effects on adherence and retention were sustained in the cash groups after the intervention was complete.Although this intervention improved adherence, the effect of such interventions should be considered along with other tested interventions as part of a comprehensive package of support during the treatment journey.A larger-scale impact evaluation to determine the effectiveness of cash support on cost-effectiveness, and issues related to sustainability, also needs consideration.
Overall, any intervention designed to influence human behaviour, such as modifying medication adherence in patients with chronic conditions, would be more successful if multiple factors that aid the change in human behaviour are addressed.Combined interventions comprise different components, which may act both independently and inter-dependently, to address the changes needed, and may be more effective than using a single component in isolation [124].However, the complexity involved in designing, implementation and replicating combined interventions often complicates the practicalities of such interventions [124].Therefore, interventions involving a single component may be preferred as they are easier to design, implement and replicate, and oftentimes are successful in influencing a behaviour change [124].

Limitations of the reviewed studies
The quality of the studies included in our review varied; almost two-thirds of the studies reviewed had a low risk of bias, while fewer than one-tenth of all studies had a high risk of bias.While most studies reviewed had a low risk of bias, our assessment of a study's quality was limited for some studies due to a failure to report critical information related to study methodologies, such as study designs, or participant inclusion criteria, or to adequately describe outcome measures.Based on the small number of studies or interventions reviewed for HPT and DM, there may have been challenges in searching and including these conditions or related interventions.In addition, one in five of the total reviewed studies did not have clearly defined outcome measures.Therefore, future studies assessing adherence to treatment should use validated adherence measures, to report reliable findings or make strong conclusions.More rigorous research in this field is critical, as is a replication of studies with positive findings in other settings.Furthermore, some of the studies described in this review were multifaceted, with some delivering multiple intervention components and others providing adherence support as a part of a broader package of services; this makes it impossible to discern the relative effect of each intervention component or identify which aspects are most impactful on adherence.Another limitation of these studies, and adherence research in general, remains with the challenge of accurately measuring medication adherence and in the variety of methodologies utilized [13].
The exclusion of data from studies conducted in North Africa may have led to the exclusion of potentially informative studies; however, NCDs are increasingly becoming the main cause of mortality in SSA, where the diseases were responsible for 37% of deaths in 2019 [20][21][22].This review was limited to studies written in English only due to authors' or reviewers' challenges in reviewing studies written in other languages.Therefore, we may have potentially excluded relevant articles written in other languages besides English.Importantly, non-English speaking countries based in SSA may provide different but useful knowledge or evidence on intervention strategies to improve adherence to treatment.Additionally, while we feel that the search terms or strings we used were able to remove irrelevant articles, it is possible that the search strings we used were not comprehensive enough.

C O N C L U S I O N S
Our study found substantial evidence of interventions to improve adherence among adults living with chronic conditions in SSA.There is more evidence that community-and home-based, mhealth and adherence counselling interventions can improve adherence to chronic conditions.These tested and evaluated adherences enhancing interventions should increasingly be considered for routine implementation in health programmes.However, rigorous ongoing evaluation of the impact and performance of these interventions will be necessary.Multifaceted adherence intervention strategies that include reliable adherence measures such as drug exposure testing and socio-economic support components such as cash vouchers provided to patients may be more effective than using a single-component intervention strategy.Therefore, evidence gaps in adherence-enhancing interventions need to be closed, including on cost-effectiveness and long-term effectiveness.Future research should seek to answer if existing intervention strategies can be successfully adapted for all chronic conditions assessed in this review.Our findings support testing more interventions and the need to develop a gold standard (or uniform measures) for adherence outcome ascertainment.

D I S C L A I M E R
The statements and views made in this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

D ATA AVA I L A B I L I T Y S TAT E M E N T
The datasets used or analysed for the current study are available from the corresponding author on reasonable request.

R E F E R E N C E S
stable ART patients who meet at facilities or community locations in groups of up to 30 every 2−3 months to receive group counselling, have a brief symptom screen and receive pre-packed medications.DMD comprises prepacking and distribution of medications to pick-up points, which are at locations other than the clinic pharmacy.Patients only need to come to the clinic on a 6-monthly basis for a clinical exam and rescripting.functioning health system working in harmony is built on having trained and motivated health workers, a well-maintained infrastructure, and a reliable supply of medicines and technologies, backed by adequate funding, strong health plans and evidenceor gifts with a definitive value provided to study participants.The voucher incentive interventions are offered and designed by the researchers or investigators to reward participants/patients for achieving a certain goal and encourage team members to exceed their goals.
Active visualization deviceA device that delivers or provides health information that could be particularly useful in educating patients about the specific condition or related treatment.
provides food and nutritional care to malnourished HIV-positive individuals as a therapeutic and supplementary feeding package at health facilities.
-E and JBFDW contributed to the conception and design of the study.SBG organized the database and performed the analysis.SBG wrote the first draft of the manuscript.SBG, JBFDW, WDFV, AMJW and STL-E wrote sections of the manuscript.All authors contributed to the manuscript revision, read and approved the submitted version.A C K N O W L E D G E M E N T SThank you to Lisa Noordman and Marit Wiltink (master's students from Utrecht University) for assisting with the screening of articles and data extraction.Lisa and Marit joined Ezintsha as part of the student internship programme between University of the Witwatersrand in South Africa and Utrecht University in the Netherlands.We also thank Mansi Agarwal from Washington University in St. Louis, United States of America for her guidance and advises during the protocol development stage.F U N D I N GThis research was supported by the Consortium for Advanced Research Training in Africa (CARTA).CARTA is jointly led by the African Population and Health Research Center and the University of the Witwatersrand.SBG was funded by the Carnegie Corporation of New York (Grant No. G-19-57145), Sida (Grant No. 54100113), Uppsala Monitoring Center, Norwegian Agency for Development Cooperation (Norad) and by the Wellcome Trust [reference no.107768/Z/15/Z] and the UK Foreign, Commonwealth & Development Office, with support from the Developing Excellence in Leadership, Training and Science in Africa (DELTAS Africa) programme.WDFV and STL-E are supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (Award Number UG3HL156388).

Table 1 . Methodological aspect of the systematic review Criteria for study inclusion Components details
The following details were extracted: study title, first author, publication year, type, study duration, country, population, study geographical setting, study design, sample size, intervention

Table 2 . Description of adherence intervention types
A device enabling healthcare professionals or researchers to interpret activities of the patient/participant in the context of adherence and inform better decision-making and as an intervention and tool for the patient to aid self-management and improve adherence.

Table 2 . (Continued)
Chair of the IAS-USA HIV drug resistance panel and as an Organizing Committee member for the international drug resistance workshop.WDFV received funding for the ADVANCE RCT through his institution from UNITAID, USAID and SAMRC, and received a study drug from ViiV Healthcare and Gilead Sciences.WDFV also reports funding for his unit from the Bill and Melinda Gates Foundation, National Institutes for Health, UNITAID, Foundation for Innovative New Diagnostics (FIND) and the Children's Investment Fund Foundation (CIFF), and received drug donations from Merck and J&J Sciences for investigatorled clinical studies.The unit leads investigator-led studies that receive financial support from Merck and ViiV and is involved in commercial drug studies for Merck.The unit performs evaluations of diagnostic devices for multiple biotech companies.WDFV also receives honoraria for educational talks and advisory board membership for Gilead, ViiV, Mylan, Merck, Adcock-Ingram, Aspen, Abbott, Roche, J&J, Sanofi and Virology Education; participates on DSMB for NIH International; is currently an unpaid board member for Dira Sengwe and was an unpaid board member for SAHCS.None of the ADVANCE RCT funders were involved in the design, execution or analysis of this study.All other authors report no potential conflicts.